title: IFN-stimulated gene expression is a useful potential molecular marker of response to antiviral treatment with Peg-IFNα 2b and ribavirin in patients with hepatitis C virus genotype 1.
abstract: OBJECTIVE
  We undertook this study to determine the baseline gene expression of IFI27, IFIT1, IFI6, ISG15, IRF-1, IRF-3, OAS-2 and CXCL10 and its usefulness as molecular markers of response to antiviral treatment with peg-IFNα 2b/RBV in patients with hepatitis C virus genotype 1 (HCV-1).
  
  
  METHODS
  Gene expression was analyzed by RT-PCR in baseline liver biopsies from 42 HCV-1 patients who were treated with Peg-IFNα 2b/RBV for 48 weeks. In addition, we investigated gene expression of these genes in a second liver biopsy obtained 24 weeks post-treatment in sustained viral response (SVR) and relapser patients.
  
  
  RESULTS
  Thirteen patients achieved SVR, four were relapsers, four patients with viral response (VR) discontinued the following for 24 weeks post-treatment and 21 patients did not respond to antiviral therapy (NR). All patients with HCV-1 showed gene overexpression in baseline liver tissue, but only IFI27, IFIT1, IFI6, ISG15, and CXCL10 showed differential gene expression, which is inversely related to the response to antiviral therapy. Thus, liver tissue of NR patients showed upregulation of these genes, whereas patients with SVR gene expression level was significantly lower. Furthermore, 24 weeks afterwards treatment, SVR patients showed a significant downregulation of such genes, which was consistent with the RNA-HCV suppression. ISGs (IFI27, IFIT1, IFI6) and chemokine CXCL10 showed the best positive and negative predictive values on SVR to IFN/RBV therapy (range: 70.8-75% and 71.43-82.35%), respectively.
  
  
  CONCLUSIONS
  IFI27, IFIT1, IFI6, ISG15, and CXCL10 genes are potential biological markers useful for predicting response to Peg-IFNα 2b/RBV therapy in HCV-1 patients.
authors.affiliation: Departamento de Gastroenterología y Hepatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zurbirán, Vasco de Quiroga No 15, México, D.F., México. ssiamx@yahoo.com.mx
authors.forename: María Sara
authors.initials: MS
authors.lastname: Sixtos-Alonso
authors.forename: Fausto
authors.initials: F
authors.lastname: Sánchez-Muñoz
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Sánchez-Ávila
authors.forename: Rosalba Avalos
authors.initials: RA
authors.lastname: Martínez
authors.forename: Aaron
authors.initials: A
authors.lastname: Domínguez López
authors.forename: Florencia
authors.initials: F
authors.lastname: Vargas Vorácková
authors.forename: Misael
authors.initials: M
authors.lastname: Uribe
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D054316:Biomarkers, Pharmacological; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons; C417083:peginterferon alfa-2b